Abstract 4145: Serum miR-21 is a promising biomarker for early detection and prognosis of colorectal cancer

Abstract

Abstract Background: MicroRNAs (miRNAs) are rapidly emerging as potential diagnostic and prognostic markers of human cancer. Recent studies indicate that tumor-derived miRNAs can also be present in human serum and plasma in remarkably stable form. Therefore, specific miRNAs that are frequently over-expressed in cancer tissues present with logical targets for the development of noninvasive miRNA biomarkers in blood. The aim of this study was to investigate whether serum miR-21 can be used as a biomarker for the earlier diagnosis and prognosis of colorectal cancer (CRC). Materials & Methods This study was divided into two steps. The first step included determination of miR-21 expression using quantitative TaqMan assays in a ‘training set’ comprised of pre-operative serum samples from 12 CRC patients and 12 healthy subjects. To enhance assay specificity, we analyzed miR-21 expression in matched CRC and normal tissues from 8 of the 12 patients. The second step included an independent confirmation of these results in a ‘validation set’ of serum samples from 184 CRC patients, 43 patients with advanced adenomas and 53 healthy controls. We then examined miR-21 expression in matched normal and cancer tissue samples from 167 CRC patients. In addition, we analyzed post-operative serum samples from 60 CRC patients. Results: In the training set, miR-21 expression was significantly up-regulated in both serum (p<0.001) and tissue samples (p<0.01) of patients with CRC compared to healthy controls. In the validation set, serum miR-21 expression levels were significantly elevated in advanced adenoma (p<0.001) and CRC (p<0.001) patients. ROC analysis revealed high sensitivity and specificity for serum miR-21 in discriminating advanced adenomas (AUC: 0.8, sensitivity: 76%, specificity: 82%) and CRC (AUC: 0.92, sensitivity: 90%, specificity: 83%) from control subjects. In addition, miR-21 levels in serum closely correlated with those in CRC tissues (p<0.001). Of interest, surgical treatment in CRC patients resulted in significantly lowered miR-21 expression levels in the post-operative serum samples (p<0.001). Higher serum miR-21 levels were associated with larger tumor size (p=0.004), distant metastases (p=0.01) and higher TNM stage (p=0.04). High expression of miR-21 in both serum and primary CRC tissues were significantly associated with poor survival (serum, p=0.005; tissue, p=0.006). Serum miR-21 was an independent prognostic marker in CRC patients (HR=4.1, p=0.03). Conclusions: Since serum miR-21 expression levels accurately discriminated between healthy subjects and patients with advanced adenomas and early CRC, it may serve as a promising diagnostic biomarker for the early detection of colorectal neoplasia. Because serum miR-21 levels were a better predictor for poor survival, detection of this non-coding miRNA in serum also has potential for development as a noninvasive prognostic biomarker in CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4145. doi:1538-7445.AM2012-4145